Many patients with Syndrome X (chest pain despite angiographically normal coronary arteries) have myocardial ischemia due to limited coronary flow reserve (microvascular angina). Although most patients respond symptomatically to calcium channel blockers and nitrates, approximately 25% continue to be significantly limited because of chest pain. In this study, we assessed the hemodynamic and symptomatic efficacy of lidoflazine, a drug that blocks calcium entry into coronary vascular smooth muscle at sites other than the slow channel (the site of activity by calcium channel blockers). To investigate the effect of lidoflazine (240-360 mg/d) on exercise tolerance and hemodynamics, 21 patients with microvascular angina, symptomatic despite prior treatment with calcium channel blockers, underwent graded exercise treadmill testing off all medication, and 3-4 weeks later, on lidoflazine. Compared to baseline, lidoflazine resulted in a 32% increase in total duration of exercise (p less than .005), and 66% increase in time to onset of chest pain (P less than .005). A trend toward higher systolic blood pressure - heart rate product (an index of myocardial oxygen demand) may indicate improved coronary blood flow and oxygen delivery during exercise stress in many patients on lidoflazine.